The long-range goal of this work is to obtain a better understanding of the molecular mechanisms involved in cell mediated immunity. Emphasis will be placed on the further characterization of the natural cytotoxicity exhibited by normal human peripheral blood lymphocytes for cultured cell lines. We have demonstrated a multiplicity of antigens recognized by natural killer (NK) cells, with some target antigens shared by allogeneic cell lines. We will attempt to purify and characterize these target antigens. The receptor sites and the lytic mechanism(s) in natural cytotoxicity will also be further investigated and compared to antibody dependent and T cell mediated cytotoxic reactions. The premise that mitogen induced lysis is largely due to enhancement of natural cytotoxicity will also be further tested, and the enhancement of natural cytotoxicity by addition of insusceptible cell lines will be studied further. In other experiments, we will continue to investigate the stimulatory capacity of cultured cell lines in the mixed lymphocyte-tumor (MLT) assay. As MLT can enhance natural cytotoxicity, it is important to determine the relative contributions of cytotoxic T lymphocytes and NK cells to the observed cytotoxicity after MLT, and methods for distinguishing these mechanisms are described herein. The apparent inverse relationship of MLT stimulatory capacity to NK susceptibility of cultured cell lines will be studied. Suppression of lymphocyte activation by a factor produced by Mycoplasma Arginini has been reported. This protein will be purified and further characterized. Finally, the utility of in vitro assays for cellular immune function (especially natural cytotoxicity) for diagnosis and immunotherapeutic drug screening will be investigated. These studies on the in vitro responses of human lymphocytes to cultured tumor cells should increase our understanding of immune surveillance.